9.

Windsor E (to Riker Laboratories). Orally active therapeutic compositions, especially polysaccharide sulfates. U.S. 3,088,868 (Cl 167-55). May 7, 1963, Appl Aug. 18, 1958. (CA59:12598d) [Therapeutic substances previously administrable in effective doses only parenterally were produced in orally effective compns. by adding an adjuvant which is a nontoxic complexing agent, such as an amino acid salt or a polyamine polyacid free of Mg++and Ca++. Thus, tri-K Versenate (tri-K salt of EDTA), di-Na Versenate, and the Na salt of N,N-dimethylglycine were mixed sep. with a fraction of sulfated polysaccharide (CA 56, 11722i) having 12 glucose units and 2.0 sulfate groups per glucose unit. The proportions of polysaccharide sulfate to adjuvant were 1:1 and 2:1. Sulfated polysaccharide was given to dogs to provide a dosage level of 100 mg./kg. and adjuvant dosages were 50 mg., and 100 mg./kg. Blood samples were taken before and 1, 2, 3, 4 and 5 hrs. after the capsule contg. the sulfated polysaccharide and adjuvant was given. The antilipemic effects were detd. Di-N Versenate (50 mg./kg.), tri-K Versenate (50 mg./kg. and 100 mg./kg.), dimethylglycine Na salt (50 mg./kg.), and sulfated polysaccharide alone resulted in 5.73, 3.74 and 5.26, 2.16, and 1.19 Grossman units, resp. (G. and Bowman, CA 48, 7103f). The polysaccharide sulfate was prepd. by adding 120 ml. of chlorosulfonic acid to 800 ml. of dry pyridine while maintaining the temp. between 10 and 20°. The mixt. was stirred for 1 hr. at room temp. Cornstarch dextrin (75 g.), having an intrinsic viscosity of 0.068 in 0.1N KOH in 200 ml. of pyridine, was added. The mixt. was heated for 10 hrs. on a steam bath with stirring, then cooled to room temp. The upper pyridine layer was decanted from the solid cake; the cake was dissolved in 400 ml. H2O, then poured into 5 l. MeOH, and the residue dissolve din 1.75 l. H2O contg. 17.5 g. NaCl. The pH was adjusted to 9 with 6N NaOH and 5.25 l. MeOH was added to ppt. the Na salt of the cornstarch dextrin sulfate which was washed with MeOH and Et2O, yielding 223.5 g. To a soln. contg. 184.5 g. of this product, 3510 ml. H2O, and 32 g. NaCl, 625 ml. acetone was added. After standing overnight at 0°, the supernatant layer was removed and discarded. The lower sirupy layer was triturated with MeOH to yield 112.7 g. of a white, granular material (59%) which had an av. mol. size of 12 glucose units, an av. mol. wt. of 4000, and 2.0 sulfate groups per glucose residue. By using the above procedure, a sample was prepd. with dry corn sirup solids. The product was pptd. with acetone to collect the fraction pptd. by between 25 and 30% by vol. of acetone. The sulfate had an av. mol. size of 11.1 glucose units/mole and contained 2.37 sulfate groups per glucose unit.]

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